Differential increase of Fas ligand expression on metastatic and thin or thick primary melanoma cells compared with interleukin-10

Fas ligand (FasL), a cell surface molecule belonging to the tumour necrosis factor family, binds to its receptor Fas and thus induces apoptosis of Fas -bearing cells such as activated lymphocytes. In this paper, we report the expression of FasL on melanoma cell lines and patient tumour specimens, and compare it with the expression of interleukin-10 (IL-10), a putative immun osuppressive factor. Apoptosis of Fas-bearing Jurkat cells was increased af ter interferon-a treatment of the FasL-positive melanoma cell line A375, su ggesting a regulation of FasL function. We also tested whether FasL and IL- 10 were ever co expressed. Immunohistochemistry studies showed that IL-10 e xpression was highly positive in the same tumour samples which expressed Fa sL. In the melanoma patients with thin primaries, 10 of the 12 primaries an d six of the seven metastatic lesions were positive for IL-10. In the melan oma patients with thick primaries (> 0.75 mm), four of the five primary les ions and nine of the 10 metastatic lesions were positive for IL-10. In cont rast, FasL was generally negative in primary tumours and positive in metast atic tumours. In the thin primary melanoma patients, two of the 12 primarie s and five of the seven metastatic tumours were positive for FasL. From the thick melanomas, one of the five primaries and five of the 10 metastatic l esions were positive for FasL. The function of melanoma derived FasL was co nfirmed by four different cytotoxicity assays. (C) 1999 Lippincott Williams & Wilkins.